Cited by 3,878Sleep and Wakefulness ResearchRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

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The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

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de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., van den Pol, A. N., Bloom, F. E., Gautvik, K. M., Sutcliffe, J. G.·1998·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.95.1.322PMC PMC18213

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Abstract

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.

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Background
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Authors: de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., van den Pol, A. N., Bloom, F. E., Gautvik, K. M., & Sutcliffe, J. G.
Affiliations: Departments of Molecular Biology and Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; Center for Sleep and Circadian Neurobiology, Stanford University, Stanford, CA 94305; Department of Neurosurgery, Yale University, New Haven, CT 06520; Institute of Basic Medical Sciences, Department of Biochemistry, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway; and The Jackson Laboratory, Bar Harbor, ME 04609
Scripps Research Institute (US)
ORCID: Kilduff, T. S.
Peyron, C.
Gao, X.-B.
Gautvik, V. T.
Frankel, W. N.
Gautvik, K. M.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1998-01-06
Volume: 95
Issue: 1
Pages: 322-327
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.95.1.322
PMC: PMC18213
OpenAlex: W2152211310
Cited by: 3,878
References: 46
Citations by year: 2026: 83 · 2025: 126 · 2024: 108 · 2023: 123 · 2022: 156 · 2021: 133 · 2020: 137 · 2019: 133 · 2018: 170 · 2017: 159 · 2016: 159 · 2015: 173 · 2014: 208 · 2013: 186 · 2012: 188
FWCI: 55.05
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders: Fondation Fyssen
Norges Forskningsråd
National Institutes of Health (5r01ns033396-03, 5p01ag011084-05)
National Institute on Aging (AG-11084)
National Institute of General Medical Sciences (GM-32355, R01GM032355)
National Institute of Neurological Disorders and Stroke (NS33396)
Army Research Office
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: orexin, hypothalamus, hypothalamic neurons, secretin, neuropeptides, neurotransmitters, hypothalamic projections, brainstem, thalamus
MeSH terms: Orexins, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Chromosomes, Homeostasis, Hypothalamus, Posterior, Male, Molecular Sequence Data, Neurons, Neuropeptides, Protein Precursors, Secretin, Synaptic Vesicles, Consensus Sequence, Rats, Wistar, Neurotransmitter Agents, Intracellular Signaling Peptides and Proteins, Mice, Rats

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The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

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